The aim is to obtain detailed understanding of changes in brain structure and function mediated by cAMP, cGMP and a specific Ca2 ion-binding protein (CDR). The role of cGMP in the regulaton of gene expression will be examined. The possibility that the defects associated with Down syndrome may be secondary to disordered or excessive cGMP during development will be analyzed, noting particularly the possible involvement of superoxide dismutase in activation of guanylate cyclase. The heat shock phenomena of Drosophila cells and of mammalian fibroblasts in culture provide model systems which will be utilized in studies of cGMP and altered patterns of protein synthesis and post-translational modification. Experiments designed to reveal interactions between Ca2 ion, CDR, cAMP, and cGMP will be conducted using intact cells of the C-6 glial tumor, primary cultures of glia and nerve ending particles. Actions of neurotransmitters, GTP and CDR are of particular concern. Possible cGMP-mediated effects on nuclear phospho-proteins will be analyzed.